期刊
NATURE CHEMICAL BIOLOGY
卷 5, 期 10, 页码 758-764出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.208
关键词
-
资金
- Europrofession Foundation
- Deutsche Krebshilfe [107875]
- Deutsche Forschungsgemeinschaft [BI 1044/2-2]
- Bundesministerium fur Bildung und Forschung (Go-Bio)
Protein phosphorylation transduces a large set of intracellular signals. One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. Previous work described an allosteric site mediating phosphorylation-dependent activation of AGC kinases. The AGC kinase PDK1 is activated by the docking of a phosphorylated motif from substrates. Here we present the crystallography of PDK1 bound to a rationally developed low-molecular-weight activator and describe the conformational changes induced by small compounds in the crystal and in solution using a fluorescence-based assay and deuterium exchange experiments. Our results indicate that the binding of the compound produces local changes at the target site, the PIF binding pocket, and also allosteric changes at the ATP binding site and the activation loop. Altogether, we present molecular details of the allosteric changes induced by small compounds that trigger the activation of PDK1 through mimicry of phosphorylation-dependent conformational changes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据